Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics

Abstract

Aging involves progressive physiological and metabolic reprogramming to adapt to gradual deterioration of organs and functions. This includes mechanisms of defense against pre-malignant transformations. Thus, certain tumors are more prone to appear in elderly patients. This is the case of the two most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Accordingly, aging hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, altered proteostasis, mitochondrial dysfunction, cellular senescence, exhaustion of stem cell niches, impaired intracellular communication, and deregulated nutrient sensing can play an important role in liver carcinogenesis in the elders. In addition, increased liver fragility determines a worse response to risk factors, which more frequently affect the aged population. This, together with the difficulty to carry out an early detection of HCC and iCCA, accounts for the late diagnosis of these tumors, which usually occurs in patients with approximately 60 and 70 years, respectively. Furthermore, there has been a considerable controversy on what treatment should be used in the management of HCC and iCCA in elderly patients. The consensus reached by numerous studies that have investigated the feasibility and safety of different curative and palliative therapeutic approaches in elders with liver tumors is that advanced age itself is not a contraindication for specific treatments, although the frequent presence of comorbidities in these individuals should be taken into consideration for their management.

Effect of Transdermal Fentanyl Patch Combined with Enhanced Recovery after Surgery on the Curative Effect and Analgesic Effect of Liver Cancer

“…The pain in liver cancer patients is mostly severe and persistent, so analgesic measures are necessary. Many liver cancer patients have pain as a result of their treatment methods and drugs, and patients experience evident pain symptoms following surgical resection of their liver cancer, which has a significant impact on their daily lives [ 23 ]. The main method for relieving the pain of patients is drug analgesia.…”

Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study

“…In our study, though great heterogeneity was found in YPs and OPs, following the traditional cutoff age at 65 years old, no differences were found in efficacy endpoints between the two groups ( Table 2 and Figure 1 ), which is consistent with most previous studies. 23 , 24 , 37 , 39 , 40 Application of ICIs in other solid tumors suggested similar long-term outcomes in aged patients, following cut-off age at 70, 75, or 80 years, 41–44 which suggested promising prospect of application of ICIs in aging patients. However, age-related decreased performance status, complicated comorbidities, decreased function of solid organs (especially for aging liver with decreased ability of metabolism), immunosenescence, etc.…”

“…Therefore, participants from clinical trials might not accurately represent realworld situation of elderly patients, especially for whose age is ≥75 years. [22][23][24] Although previous studies have already investigated the application of sorafenib, lenvatinib monotherapy, or A+T in elderly patients with uHCC, [25][26][27][28] whether this group of patients would benefit from sorafenib or lenvatinib plus PD-1 inhibitors, needs to be clarified. In order to explore the efficacy and safety of sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients with uHCC, we conducted this study.…”

The prognostic role of controlling nutritional status and skeletal muscle mass in patients with hepatocellular carcinoma after curative treatment

“…Sarcopenia is a prognostic factor following liver resection and ablation therapy in patients with HCC [19,20]. Elderly patients who receive treatment for HCC are increasing [21] and also suffer complications of primary (age-related) sarcopenia and/or secondary (cancer-related or cirrhosis) sarcopenia.…”